Rapid and specific detections of biomolecules and biological cells, such as proteins, DNAs, and RNAs, viruses, peptides, antibodies, antigens, red blood cells, white blood cells, and platelets, have become more and more important to biological assays crucial to fields such as genomics, proteomics, diagnoses, and pathological studies. For example, the rapid and accurate detection of specific antigens and viruses is critical for combating pandemic diseases such as AIDS, flu, and other infectious diseases. Also, due to faster and more specific methods of separating and detecting cells and biomolecules, the molecular-level origins of disease are being elucidated at a rapid pace, potentially ushering in a new era of personalized medicine in which a specific course of therapy is developed for each patient. To fully exploit this expanding knowledge of disease phenotype, new methods for detecting multiple biomolecules (e.g., viruses, DNAs and proteins) simultaneously are increasingly desired and required. The multiplex biomolecule detection methods must be rapid, sensitive, highly parallel, and ideally capable of diagnosing cellular phenotype in vivo.
A specific type of biological assay increasingly used for medical diagnostics, as well as in food and environmental analysis, is immunoassay. An immunoassay is a biochemical test that measures the level of a substance in a biological liquid, such as serum or urine, using the reaction of an antibody its antigen. The assay takes advantage of the specific binding of an antibody to its antigen. Monoclonal antibodies are often used as they only usually bind to one site of a particular molecule, and therefore provide a more specific and accurate test, which is less easily confused by the presence of other molecules. The antibodies picked must have a high affinity for the antigen (if there is antigen available, a very high proportion of it must bind to the antibody). In an immunoassay, both the presence of antigen or antibodies can be measured. For instance, when detecting infection the presence of antibody against the pathogen is measured. For measuring hormones such as insulin, the insulin acts as the antigen.
Conventionally, for numerical results, the response of the fluid being measured must be compared to standards of a known concentration. This is usually done though the plotting of a standard curve on a graph, the position of the curve at response of the unknown is then examined, and so the quantity of the unknown found. The detection of the quantity present of antibody or antigen can be achieved by a variety of methods. One of the most common is to label either the antigen or antibody. The label may consist of an enzyme, radioisotopes, or a fluorophore.
A specific phenomenon that has been used in photo detection is photo-induced, or photo-activated, charge separation, which is the process of an electron in an atom being excited to a higher energy level and then leaving the atom to a nearby electron acceptor. Upon exposure to various radiation, electrons in many materials are capable of being excited and moved into another energy level. Specific materials suitable for photo-induced charge separation and for use in detection include dyes, photoactive polymers, quantum dots. Conventional detection devices involving photo-induced charge separation, however, usually are large in size and not suitable for inclusion in an integrated device.
An increasing amount of biological assays, such as immunoassays and gene sequencing, are being carried out on microarrays, such as DNA microarrays or protein microarrays. A microarray is a collection of microscopic spots, such as DNA or protein spots attached to a solid surface, such as glass, plastic or silicon chip forming an array. The microarrays can be used to measure the expression levels of large numbers of genes or proteins simultaneously. The biomolecules, such as DNAs or proteins, on microarray chip typically are detected through optical readout of fluorescent labels attached to a target molecule that is specifically attached or hybridized to a probe molecule. These optical methods are difficult to implement and miniaturize because they rely on the use of optical labels and require large or expensive instrumentation.
A field effect transistor (FET) is a transistor that relies on an electric field to control the conductivity of a channel in a semiconductor material. An FET has three terminals, which are known as the gate, drain and source. A voltage applied between the gate and source terminals modulates the current between the source and drain terminals. A small change in gate voltage can cause a large variation in the current from the source to the drain, thus enabling the FET to amplify signals.
FETs are commonly used for weak-signal amplification and can amplify analog or digital signals. They are also sometimes used as voltage-controlled resistors. Recently, FETs have been explored as sensors in chemical and biological detection. However, the detection sensitivity of current FETs is relatively low as compared to traditional photonic based detectors.